We propose to study the mechanisms that regulate the tolerance and autoimmunity to a major, dominant idiotype (Id). Id is a specific determinant present on variable regions of lymphocyte antigen receptors as well as on the specific lymphocyte products. A major Id is the one expressed on a majority of lymphocytes of given immunological specificity in all members of an inbred animal population. We will study the T15 of BALB/c mice, as an experimental model. T15 is present on both lymphocytes and antibody against phosphorycholine (PC), a hapten carried on the cell wall polysaccharide of S. pneumoniae R36a (Pn). T15 is expressed and synthesized in normal adult mice, i.e., it is tolerated by the mouse's own immune system. However, recent studies from several laboratories, including ours, demonstrated that immunization of BALB/c mice with Pn resulted in activation of spontaneous, autoimmune anti-T15 response that appears to regulate the T15+, Pn-reactive B cells. In order to understand the immunoregulative role of such autologous anti-Id response one must elucidate the mechanisms of its generation. Our first goal is to characterize the cells with receptor for T15 that are activated by, and that follow the cyclical immune response to Pn in a reciprocal fashion. We will determine the phenotypic properties of anti-T5 cells and their ability to suppress and/or enhance the activity of T15+ lymphocytes in vivo and in vitro both in the presence of Pn antigen and independently of it. We will study functional interactions between anti-T15 cells, soluble T15 (i.e., the Pn-specific antibody) and Pn-specific regulatory cells in the regulation of the T15+, Pn-responsive clone. Secondly, we will test various hypotheses that may explain the autoimmunogenicity of T15 following receptor-Pn interaction, presentation of T15 on various cells, etc. The possible role of other self determinants, in particular, products of MHC genes in recognition and differentiation of T15 will also be studied.